Chemoregimen - Lung Cancer

Lung Cancer

Non-small cell lung cancer
Induction chemoradiation and adjuvant chemotherapy for superior sulcus cancer
Adjuvant chemotherapy for stage II and IIIA cancer
Concurrent chemoradiation for stage III cancer
Chemotherapy for stage IV (metastatic) cancer

Small cell lung cancer
Limited stage
Extensive stage

Non-small cell lung cancer

Induction chemoradiation and adjuvant chemotherapy for superior sulcus cancer

Induction chemoradiation
Cisplatin (CDDP) 50 mg/m2 iv d1, 8, 29 and 36
Etoposide (VP-16) 50 mg/m2 iv d1-5 and 29-33
Radiotherapy 1.8 Gy/d over 5 weeks to 45 Gy

Surgical resection 3-5 weeks later

Adjuvant chemotherapy
Cisplatin (CDDP) 50 mg/m2 iv d1, 8, 29 and 36
Etoposide (VP-16) 50 mg/m2 iv d1-5 and 29-33

Rusch VW et al. Induction chemoradiation and surgical resection for superior sulcus non-small-cell lung cancinomas: long-term results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160). J Clin Oncol 2007; 25:313 (link to the article).

Adjuvant chemotherapy for stage II and IIIA cancer (link to Cancer Care Ontario and ASCO guideline)

Cisplatin + Etoposide or Vinorelbine or Vinblastine or Vindesine
Cisplatin 50 mg/m2 iv d1 and 8 q4w x 4 cycles, or

80 mg/m2 iv d1 q3w x 4 cycles, or

100 mg/m2 iv d1 q4w x 3-4 cycles, or

120 mg/m2 iv d1 q4w x 3 cycles

plus

Etoposide 100 mg/m2/d iv d1-3 q3-4w till completion of cisplatin, or

Vinorelbine 25-30 mg/m2 iv qw till completion of cisplatin, or

Vinblastine 4 mg/m2 iv qw d1-29, then q2w after d43 till completion of cisplatin, or

Vindesine 3 mg/m2 iv qw d1-29, then q2w after d43 till completion of cisplatin

Pignon JP et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol 2008; 26:3552 (link to the article).

Fruh M et al. Pooled analysis of the effect of age on adjuvant cisplatin-based chemotherapy for completely resected non-small-cell lung cancer. J Clin Oncol 2008; 26:3573 (link to the article).

Chevalier TL et al. Long-term results of the International Adjuvant Lung Cancer Trial (IALT) evaluating adjuvant cisplatin-based chemotherapy in resected non-small cell lung cancer (NSCLC). 2008 ASCO annual meeting. Abstract 7507 (link to the abstract).

Pepe C et al. Adjuvant vinorelbine and cisplatin in elderly patients: National Cancer Institute of Canada and Intergroup Study JBR.10. J Clin Oncol 2007; 25:1553 (link to the article).

Douillard J et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomized controlled trial. Lancet Oncol 2006; 7:719 (link to the article).

Winton T et al. Vinorelbine plus cisplatin vs. observation in resected non-small cell lung cancer. N Engl J Med 2005; 352:2589 (link to the article).

Arriagada R et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Eng J Med 2004; 350:351 (link to the article).

Carboplatin + Paclitaxel
Carboplatin (Paraplatin) AUC 6 iv d1
Paclitaxel (Taxol) 200 mg/m2 iv d1
Q3w x 4 cycles

Strauss GM et al. Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): update of Cancer and Leukemia Group B (CALGB) protocol 9633. 2006 ASCO annual meeting. Abstract 7007 (link to the abstract).

Strauss GM et al. Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection of stage IB non-small cell lung cancer (NSCLC): report of Cancer and Leukemia Group B (CALGB) protocol 9633. 2004 ASCO annual meeting. Abstract 7019 (link to the abstract).

Concurrent chemoradiation for stage III cancer (back to top)

Cisplatin + Etoposide + RT
Cisplatin (CDDP) 50 mg/m2 iv days 1, 8, 29 and 36
Etoposide (VP-16) 50 mg/2 iv days 1-5, 29-33
Radiotherapy 1.8 Gy/d to 45 Gy
If no disease progression, continue radiotherapy 2 Gy/d to 61Gy

Hanna NH et al. Phase III trial of cisplatin (P) plus etoposide (E) plus concurrent chest radiation with or without consolidation docetaxel (D) in patients (pts) with inoperable stage III non-small cell lung cancer (NSCLC): HOG LUN 01-24/USO-023. 2007 ASCO annual meeting. Abstract 7512 (link to the abstract).

Gandara DR et al. Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB non-small cell lung cancer: phase II Southwest Oncology Group Study S9504. J Clin Oncol 2003; 21:2004 (link to the article).

Weekly Carboplatin + Paclitaxel + RT →Carboplatin + Paclitaxel
Paclitaxel (Taxol) 45-50 mg/m2 iv over 1 h qw x 7 weeks
Carboplatin (Paraplatin) AUC 2 iv over 30 min qw x 7 weeks
Radiotherapy 2 Gy/d to 63-66 Gy over 7 weeks
3 weeks later
Paclitaxel (Taxol) 200 mg/m2 iv over 3 hrs q3w x 2 cycles
Carboplatin (Paraplatin) AUC 6 iv over 30 min q3w x 2 cycles

Belani CP et al. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: A randomized phase II locally advanced multi-modality protocol. J Clin Oncol 2005; 23:5883 (link to the article).

Choy H et al. Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer. J Clin Oncol 1998; 16:3316 (link to the article).

Chemotherapy for stage IV (metastatic) cancer (back to top)

Cisplatin + Paclitaxel
Regimen 1
Paclitaxel (Taxol) 135 mg/m2 iv over 24 hours day 1
Cisplatin (CDDP) 75 mg/m2 iv day 2
Q3w

Schiller JH et al. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Eng J Med 2002; 346:92 (link to the article).

Regimen 2
Paclitaxel (Taxol) 175 mg/m2 iv over 3 hours day 1
Cisplatin (CDDP) 70 mg/m2 iv day 1
Q3w x 4 cycles

Park JO et al. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non-small-cell lung cancer. J Clin Oncol 2007; 25:5233 (link to the article).

Cisplatin + Gemcitabine
Regimen 1
Cisplatin (CDDP) 100 mg/m2 iv day 1
Gemcitabine (Gemzar) 1000 mg/2 iv days 1, 8, 15
Q4w

Schiller JH et al. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Eng J Med 2002; 346:92 (link to the article).

Regimen 2 (for elderly patients > 70 years of age)
Cisplatin (CDDP) 60 mg/m2 iv day 1
Gemcitabine (Gemzar) 1000 mg/m2 iv days 1, 8
Q3w

Gridelli C et al. Cisplatin plus gemcitabine or vinorelbine for elderly patients with advanced non-small-cell lung cancer: the MILES-2P studies. J Clin Oncol 2007; 25:4663 (link to the article).

Cisplatin + Docetaxel
Cisplatin (CDDP) 75 mg/m2 iv day 1
Docetaxel (Taxotere) 75 mg/m2 iv day 1
Q3w

Fossella F et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small cell lung cancer: the TAX 326 study group. J Clin Oncol 2003; 21:3016 (link to the article).

Schiller JH et al. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Eng J Med 2002; 346:92 (link to the article).

Carboplatin + Paclitaxel
Regimen 1
Carboplatin (Paraplatin) AUC 5-6 iv day 1
Paclitaxel (Taxol) 175-225 mg/m2 iv over 3 hours day 1
Q3w

Lilenbaum R et al. Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2. J Clin Oncol 2008; 26:863 (link to the article).

Schiller JH et al. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Eng J Med 2002; 346:92 (link to the article).

Regimen 2
Carboplatin (Paraplatin) AUC 6 iv day 1
Paclitaxel (Taxol) 100 mg/m2 iv qw x 3
Premedications for paclitaxel:
Dexamethasone (Decadron) 20 mg iv
Diphenhydramine (Benadryl) 50 mg iv
Cimetidine (Tagamet) 300 mg iv or Ranitidine (Zantac) 50 mg iv
If no hypersensitivity reaction to paclitaxel during the first cycle, may change premedications to:
Dexamethasone (Decadron) 8-10 mg iv
Diphenhydramine (Benadryl) 25 mg iv
Cimetidine (Tagamet) 300 mg iv or Ranitidine (Zantac) 50 mg iv
Q4w x 4 cycles
Maintenance Paclitaxel 70 mg/m2 iv qw x 3 every 4 weeks with premedications as above until disease progression or intolarable toxicity

Belani CP et al. Randomized, phase III study of weekly paclitaxel in combination with carboplatin versus standard every-3-weeks administration of carboplatin and paclitaxel for patients with previously untreated advanced non-small-cell lung cancer. J Clin Oncol 2008; 26:468 (link to the article).

Carboplatin + Docetaxel
Carboplatin (Paraplatin) AUC 6 iv day 1
Docetaxel (Taxotere) 75 mg/m2 iv day 1
Q3w

Carboplatin + Gemcitabine
Carboplatin (Paraplatin) AUC 5 iv day 1
Gemcitabine (Gemzar) 1250 mg/m2 iv days 1, 8
Q3w

Sederholm C et al. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-call lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol 2005; 23:8380 (link to the article).

Cisplatin + Vinorelbine
Regimen 1
Cisplatin (CDDP) 100 mg/m2 iv d1 q4w
Vinorelbine (Navelbine) 25 mg/m2 iv over 10 min qw

Smith TJ et al. Economic evaluation of a randomized clinical trial comparing vinorelbine, vinorelbine plus cisplatin, and vindesine plus cisplatin for non-small cell lung cancer. J Clin Oncol 1995; 13:2166 (link to the article).

Regimen 3 (for elderly patients > 70 years of age)
Cisplatin (CDDP) 40 mg/m2 iv day 1
Vinorelbine (Navelbine) 25 mg/m2 iv days 1, 8
Q3w

Gridelli C et al. Cisplatin plus gemcitabine or vinorelbine for elderly patients with advanced non-small-cell lung cancer: the MILES-2P studies. J Clin Oncol 2007; 25:4663 (link to the article).

Carboplatin + Vinorelbine
Carboplatin (Paraplatin) AUC 5 iv day 1
Vinorelbine (Navelbine) 30 mg/m2 iv day 1 and 8
Q3w

Tan EH et al. Randomized study of vinorelbine-gemcitabine versus vinorelbine-carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer 2005; 49:233 (link to the article).

Gemcitabine + Docetaxel
Gemcitabine (Gemzar) 1100 mg/m2 iv d 1 and 8
Docetaxel (Taxotere) 100 mg/m2 iv day 8
Q3w
G-CSF support d 9-15

Georgoulias V et al. Platinum-based and non-platinum-based chemotherapy in advanced non-small cell lung cancer: a randomized multucenter trial. Lancet 2001; 357:1478 (link to the article).

Gemcitabine + Vinorelbine
Gemcitabine (Gemzar) 1000-1200 mg/m2 iv d 1 and 8
Vinorelbine (Navelbine) 25-30 mg/m2 iv d 1 and 8
Q3w

Tan EH et al. Randomized study of vinorelbine-gemcitabine versus vinorelbine-carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer 2005; 49:233 (link to the article).

Frasci G et al. Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small cell lung cancer. J Clin Oncol 2000; 18:2529 (link to the article).

Carboplatin + Pemetrexed
Carboplatin (Paraplatin) AUC 5 iv d1
Pemetrexed (Alimta) 500 mg/m2 iv over 10 min d1
Q3w x 4 cycles

Start vitamin supplements 1 week before initial dose of pemetrexed until 21 days after last dose of pemetrexed. Folic acid 350-1000 mcg po qd. Vitamin B12 1000 mcg I.M. every 9 weeks.

Dexamethasone 4 mg twice daily the day before, the day of and the day after pemetrexed

Gronberg BH et al. Pemetrexed + carboplatin versus gemcitabine + carboplatin in the treatment of stage IIIB/IV non-small cell lung cancer. 2007 ASCO annual meeting. Abstract 7517 (link to the abstract).

Cisplatin + Pemetrexed (especially for adenocarcinoma and large-cell carcinoma)
Cisplatin (CDDP) 75 mg/m2 iv d1
Pemetrexed (Alimta) 500 mg/m2 iv over 10 min d1
Q3w x 6 cycles

Start vitamin supplements 1 week before initial dose of pemetrexed until 21 days after last dose of pemetrexed. Folic acid 350-1000 mcg po qd. Vitamin B12 1000 mcg I.M. every 9 weeks.

Dexamethasone 4 mg twice daily the day before, the day of and the day after pemetrexed

Scagliotti GV et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008; 26:3543 (link to the article).

Carboplatin + Paclitaxel + Bevacizumab
Paclitaxel (Taxol) 200 mg/m2 iv d1 q3w x 6 cycles
Carboplatin (Paraplatin) AUC 6 iv d1 q3w x 6 cycles
Bevacizumab (Avastin) 15 mg/kg iv d1 q3w till disease progression

Approved by FDA on 10/11/2006

Ramalingam SS et al. Outcomes for elderly, advanced-stage non-small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol 2008; 26:60 (link to the article).

Sandler, A et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Eng J Med 2006; 355: 2542 (link to the article).

Johnson DH, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small cell lung cancer. J Clin Oncol 2004; 22:2184 (link to the article).

Cisplatin + Gemcitabine + Bevacizumab
Cisplatin (CDDP) 80 mg/m2 iv d1q3w x 6 cycles
Gemcitabine (Gemzar) 1250 mg/m2 iv d1, 8 q3w x 6 cycles
Bevacizumab (Avastin) 7.5-15 mg/kg iv q3w till disease progression

Manegold C et al. Randomized, double-blinded multicentre phase III study of bevacizumab in combination with cisplatin and gemcitabine in chemotherapy-naive patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC): B017704. 2007 ASCO annual meeting. LBA7514 (link to the abstract).

Cisplatin + Vinorelbine + Cetuximab (for EGFR IHC-positive patients who are not eligible for bevacizumab)
Cisplatin (CDDP) 80 mg/m2 iv d1 q3w x 6 cycles
Vinorelbine (Navelbine) 25 mg/m2 iv d1, 8 q3w x 6 cycles
Cetuximab (Erbitux) 400 mg/m2 iv loading, followed by 250 mg/m2 iv qw until progression or limiting toxicity

Pirker R et al. FLEX: a randomized, multicenter, phase III study of cetuximab in combination with cisplatin/vinorelbine (CV) versus CV alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). 2008 ASCO annual meeting. Abstract 3 (link to the abstract).

Paclitaxel + Carboplatin + Gemcitabine
Paclitaxel (Taxol) 200 mg/m2 iv d1
Carboplatin (Paraplatin) AUC 6 iv d1
Gemcitabine (Gemzar) 1000 mg/m2 iv d1 and 8
Q3w x 6 cycles

Paccagnella A et al. Adding gemcitabine to paclitaxel/carboplatin combination increases survival in advanced non-small-cell lung cancer. Results of a phase II-III study. J Clin Oncol 2006; 24:681 (link to the article).

Paclitaxel
Paclitaxel (Taxol)
Regimen 1 (q3w)
200 mg/m2 iv q3w

Tester WJ et al. Phase II study of patients with metastatic non-small cell carcinoma of the lung treated with paclitaxel by 3-hour infusion. Cancer 1997; 79:724 (link to the article).

Regimen 2 (qw)
90 mg/m2 iv qw x 6 wks every 8 wks

Fidias P et al. A phase II study of weekly paclitaxel in elderly patients with advanced non-small cell lung cancer. Clin Cancer Res 2001; 7:3942 (link to the article).

Docetaxel
Docetaxel (Taxotere)
Regimen 1
35 mg/m2 iv qw x 3 weeks every 4 weeks

Chen YM et al. A randomized trial of different decetaxel schedules in non-small cell lung cancer patients who failed previous platinum-based chemotherapy. Chest 2006; 129:1031 (link to the article).

Schuette W et al. Phase III study of second-line chemotherapy for advanced non-small-cell lung cancer with weekly compared with 3-weekly docetaxel. J Clin Oncol 2005; 23:8389 (link to the article).

Regimen 2
36 mg/m2 iv qw x 6 weeks every 8 weeks

Hainsworth JD et al. Weekly docetaxel in the treatment of elderly patients with advanced non-small cell lung cancer. Cancer 2000; 89:328 (link to the article).

Regimen 3
75 mg/m2 iv q3w

Fidias P et al. Phase III study of immediate versus delayed docetaxel after induction therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer: updated report with survival. 2007 ASCO annual meeting. LBA7516 (link to the abstract).

Ramlau R et al. Phase III study comparing oral topotecan to intravenous docetaxel in patients with pretreated advanced non-small-cell lung cancer. J Clin Oncol 2006; 24:2800 (link to the article).

Chen YM et al. A randomized trial of different decetaxel schedules in non-small cell lung cancer patients who failed previous platinum-based chemotherapy. Chest 2006; 129:1031 (link to the article).

Schuette W et al. Phase III study of second-line chemotherapy for advanced non-small-cell lung cancer with weekly compared with 3-weekly docetaxel. J Clin Oncol 2005; 23:8389 (link to the article).

Docetaxel + Bevacizumab
Docetaxel (Taxotere) 75 mg/m2 iv over 1 hour
Bevacizumab (Avastin) 15 mg/kg iv
Q3w until progression or 52 weeks of treatment

Herbst RS et al. Phase II study of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non-small-cell lung cancer. J Clin Oncol 2007; 25:4743 (link to the article).

Gemcitabine
Gemcitabine (Gemzar)
Regimen 1
1000 mg/m2 iv d 1, 8 and 15
Q4w

Manegold C et al. Single-agent gemcitabine versus cisplatin-etoposide: early results of a randomized phase II study in locally advanced or metastatic non-small cell lung cancer. Ann Oncol 1997; 8: 525 (link to the article).

Regimen 2
1250 mg/m2 iv over 30-60 min d1, 8
Q3w x 6 cycles

Vinorelbine
Vinorelbine (Navelbine) 25 mg/m2 iv qw

Furuse K et al. Randomized study of vinorelbine (VRB) versus vindesine (VDS) in previously untreated stage IIIB or IV non-small cell lung cancer (NSCLC). The Japan Vinorelbine Lung Cancer Cooperative Study Group. Ann Oncol 1996; 7: 815 (link to the article).

Topotecan IV
Topotecan (Hycamtin) 1.5 mg/m2/d iv d1-5 q3w

Perez-Soler R et al. Phase II study of topotecan in patients with advanced non-small cell lung cancer previously untreated with chemotherapy. J Clin Oncol 1996; 14: 503 (link to the article).

Topotecan PO
Topotecan (Hycamtin) 2.3 mg/m2/d po d1-5 q3w

Ramlau R et al. Phase III study comparing oral topotecan to intravenous docetaxel in patients with pretreated advanced non-small-cell lung cancer. J Clin Oncol 2006; 24:2800 (link to the article).

Pemetrexed
Pemetrexed (Alimta) 500 mg/m2 iv over 10 min q3w

Start vitamin supplements 1 week before initial dose of pemetrexed until 21 days after last dose of pemetrexed. Folic acid 350-1000 mcg po qd. Vitamin B12 1000 mcg I.M. every 9 weeks.

Dexamethasone 4 mg twice daily the day before, the day of and the day after pemetrexed.

Hanna N et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small cell lung cancer previously treated with chemotherapy. J Clin Oncol 2004; 22:1589 (link to the article).

Pemetrexed + Bevacizumab
Pemetrexed (Alimta) 500 mg/m2 iv over 10 min
Bevacizumab (Avastin) 15 mg/kg iv
Q3w until progression or 52 weeks of treatment

Start vitamin supplements 1 week before initial dose of pemetrexed until 21 days after last dose of pemetrexed. Folic acid 350-1000 mcg po qd. Vitamin B12 1000 mcg I.M. every 9 weeks.

Dexamethasone 4 mg twice daily the day before, the day of and the day after pemetrexed.

Chemotherapy + Maintenance Pemetrexed
Chemotherapy x 4 cycles, followed by pemetrexed (Alimta) 500 mg/m2 iv over 10 min q3w until progression or unacceptable toxicity

Start vitamin supplements 1 week before initial dose of pemetrexed until 21 days after last dose of pemetrexed. Folic acid 350-1000 mcg po qd. Vitamin B12 1000 mcg I.M. every 9 weeks.

Dexamethasone 4 mg twice daily the day before, the day of and the day after pemetrexed.

Ciuleanu TE et al. Maintenance pemetrexed plus best supportive care (BSC) versus placebo plus BSC: a phase III study. 2008 ASCO annual meeting. Abstract 8011 (link to the abstract).

Erlotinib
Erlotinib (Tarceva) 150 mg po qd at least 1 hour before or 2 hours after a meal

Wheatley-Price P et al. Erlotinib for advanced non-small-cell lung cancer in the elderly: an analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 2008; 26:2350 (link to the article).

Bezjak A et al. Symptom improvement in lung cancer patients treated with erlotinib: quality of life analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 2006; 24:3831 (link to the article).

Shepherd FA et al. Erlotinib in previously treated non-small-cell lung cancer. N Eng J Med 2005: 353:123 (link to the article).

Erlotinib + Bevacizumab
Erlotinib (Tarceva) 150 mg po qd at least 1 hour before or 2 hours after a meal
Bevacizumab (Avastin) 15 mg/kg iv q3w
Continue until progression or 52 weeks of treatment

Gefitinib
Gefitinib (Iressa) 250-500 mg po qd until progression or unacceptable toxicity

Sequist LV et al. First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations. J Clin Oncol 2008; 26:2442 (link to the article).

Cappuzzo F et al. Prospective study of gefitinib in epidermal growth factor receptor fluorescence in site hybridization-positive/phospho-akt-positive or never smoker patients with advanced non-small-cell lung cancer: The ONCOBELL trial. J Clin Oncol 2007; 25:2248 (link to the article).

Niho S et al. Results of a randomized phase III study to compare the overall survival of gefitinib (iressa) versus docetaxel in Japanese patients with non-small-cell lung cancer who failed one or two chemotherapy regimens. 2007 ASCO annual meeting. Abstract LBA 7509 (link to the abstract).

Inoue A et al. Prospective phase II study of gefitinib for chemotherapy-naive patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations. J Clin Oncol 2006; 24:3340 (link to the article).

West HL et al. Gefitinib therapy in advanced bronchioloalveolar carcinoma: Southwest Oncology Group Study S0126. J Clin Oncol 2006; 24:1807 (link to the article).

Chemotherapy + Maintenance Gefitinib
Chemotherapy for 3 cycles followed by
Gefitinib (Iressa) 250 mg po qd

Hida T et al. Randomized phase III study of platinum-doublet chemotherapy followed by gefitinib versus continued platinum-doublet chemotherapy in patients (pts) with advanced non-small cell lung cancer (NSCLC): results of West Japan Thoracic Oncology Group trial (WJTOG0203). 2008 ASCO annual meeting. LBA8012 (link to the abstract).

Sunitinib
Sunitinib (Sutent) 50 mg po qd for 4 weeks every 6 weeks

Socinski MA et al. Multicenter, phase II trial of sunitinib in previously treated, advanced non-small-cell lung cancer. J Clin Oncol 2008; 26:650 (link to the article).

Cetuximab
Cetuximab (Erbitux) 400 mg/m2 iv over 2 hrs first week, followed by 250 mg/m2 iv over 1 h qw

Hanna N et al. Phase II trial of cetuximab in patients with previously treated non-small-cell lung cancer. J Clin Oncol 2006; 24:5253 (link to the article).

Small cell lung cancer (back to top)

Limited stage

Cisplatin + Etoposide + RT
Regimen 1
Cisplatin (CDDP) 60 mg/m2 iv d1
Etoposide (VP-16) 120 mg/m2/d iv d1-3
Q3w x 4 cycles
Radiotherapy 1.8 Gy once daily to 54-61Gy or 1.5 Gy twice daily to 45 Gy

Turrisi AT 3rd et al. Twice daily compared with once daily thoracic radiotherapy in limited small cell lung cancer treated concurrently with cisplatin and etoposide. N Eng J Med 1999; 340:265 (link to the article).

Regimen 2
Cisplatin (CDDP) 80 mg/m2 iv d1
Etoposide (VP-16) 100 mg/m2/d iv d1-3
Q4w x 4 cycles
Radiotherapy 1.5 Gy twice daily to 45 Gy

Takada M et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japanese Clinical Oncology Group Study 9104. J Clin Oncol 2002; 20:3054 (link to the article).

Cisplatin + Etoposide + RT→Cisplatin + Irinotecan
Cisplatin (CDDP) 80 mg/m2 iv d1
Etoposide (VP-16) 100 mg/m2 iv d1-3
Radiotherapy 1.5 Gy twice daily to 45 Gy
4 weeks later
Cisplatin (CDDP) 60 mg/m2 iv d1
Irinotecan (Camptosar, CPT-11) 60 mg/m2 iv d1, 8 and 15
Q4w x 3 cycles

saito H et al. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol 2006; 24:5247 (link to the article).

Extensive stage (back to top)

Carboplatin + Etoposide
Regimen 1
Carboplatin (Paraplatin) 300 mg/m2 iv d1
Etoposide (VP-16) 100 mg/m2/d iv d1-3
Q4w x 4 cycles

Smith IE et al. Carboplatin (paraplatin; JM8) and etoposide (VP16) as first-line combination therapy for small-cell lung cancer. J Clin Oncol 1987; 5:185 (link to the article).

Regimen 2
Carboplatin (Paraplatin) AUC 5 iv d1
Etoposide (VP-16) 100 mg/m2/d iv d1-3
Q4w x 6 cycles

Quoix E et al. Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: a phase II study. Ann Oncol 2001; 12:957 (link to the article).

Regimen 3
Carboplatin (Paraplatin) AUC 5 iv over 1 h d1
Etoposide (VP-16) 140 mg/m2/d iv over 90 min d1-3
Q3w

Schmittel A et al. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol 2006; 17:663 (link to the article).

Regimen 4
Carboplatin (Paraplatin) AUC 5 iv d1
Etoposide (VP-16) 80 mg/m2/d iv d1-3
Filgrastim (Neupogen) support
Q3-4 w x 4 cycles

Okamoto H et al. Randomized phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer 2007; 97:162 (link to the article).

Cisplatin + Etoposide
Regimen 1
Cisplatin (CDDP) 80 mg/m2 iv d1
Etoposide (VP-16) 80 mg/m2/d iv d1-3
Q3w

Ihde DC et al. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small cell lung cancer. J Clin Oncol 1994; 12:2022 (link to the article).

Regimen 2
Cisplatin (CDDP) 80 mg/m2 iv d1
Etoposide (VP-16) 100 mg/m2/d iv d1-3
Q3w x 4 cycles

Natale RB et al. S0124: a randomized phase III trial comparing irinotecan/cisplatin (IP) with etoposide/cisplatin (EP) in patients (pts) with previously untreated extensive stage small cell lung cancer (E-SCLC). 2008 ASCO annual meeting. Abstract 7512 (link to the abstract).

Echcrdt JR et al. Open-label, multicenter, randomized, phase III study comparing oral topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapy-naive patients with extensive-disease small-cell lung cancer. J Clin Oncol 2006; 24:2044 (link to the article).

Noda K et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Eng J Med 2002; 346:85 (link to the article).

Regimen 3
Cisplatin (CDDP) 60 mg/m2 iv d1
Etoposide (VP-16) 120 mg/m2/d iv d1-3
Q3w

Hanna N et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol 2006; 24:2038 (link to the article).

Regimen 4
Cisplatin (CDDP) 25 mg/m2/d iv d1-3
Etoposide (VP-16) 80 mg/m2/d iv d1-3
Filgrastim (Neupogen) support
Q3-4w x 4 cycles

Cisplatin + Irinotecan
Regimen 1
Cisplatin (CDDP) 60 mg/m2 iv d1
Irinotecan (Camptosar, CPT-11) 60 mg/m2 iv d1, 8 and 15
Q4w x 4 cycles

Noda K et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Eng J Med 2002; 346:85 (link to the article).

Regimen 2
Cisplatin (CDDP) 30 mg/m2 iv d1, 8
Irinotecan (Camptosar, CPT-11) 65 mg/m2 iv d1, 8
Q3w

Carboplatin + Irinotecan
Regimen 1
Carboplatin (Paraplatin) AUC 5 iv over 1 h d1
Irinotecan (Camptosar, CPT-11) 50 mg/m2 iv over 30 min d1, 8, 15
Q4w

Regimen 2
Carboplatin (Paraplatin) AUC 4 iv d1
Irinotecan (Camptosar, CPT-11) 175 mg/m2 iv d1
Q3w x 4 cycles

Hermes A et al. A randomized phase III trial of irinotecan plus carboplatin versus etoposide plus carboplatin in patients with small cell lung cancer, extensive disease (SCLC-ED): IRIS-study. 2007 ASCO annual meeting. Abstract 7523 (link to the abstract).

Cisplatin + Topotecan
Topotecan (Hycamtin) 1.7 mg/m2/d po d1-5
Cisplatin (CDDP) 60 mg/m2 iv d5
Q3w x 4 cycles

Carboplatin + Paclitaxel
Carboplatin (Paraplatin) AUC 2 iv over 15-30 min
Paclitaxel (Taxol) 80 mg/m2 iv over 1 hour
Days 1,8,15
Q4w x 6 cycles

Neubauer M et al. Results of a phase II study of weekly paclitaxel plus carboplatin in patients with extensive small-cell lung cancer with Eastern Cooperative Oncology Group performance status of 2, or age > 70 years. J Clin Oncol 2004; 22:1872 (link to the article).

ICE-V
Day 1
Ifosfamide 5 g/m2 iv over 24 hours with mesna
Carboplatin (Paraplatin) 300 mg/m2 iv
Etoposide (VP-16) 120 mg/m2 iv
Day 2
Etoposide (VP-16) 120 mg/m2 iv
Day 3
Etoposide (VP-16) 240 mg/m2 po
Day 14
Vincristine 1 mg/m2 iv
Q4w x 6 cycles

Thatcher N et al. Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard chemotherapy in patients with small-cell lung cancer and good performance status: clinical and quality-of-life results of the British Medical Research Council multicenter randomized LU21 trial. J Clin Oncol 2005; 23:8371 (link to the article).

Etoposide
Etoposide (VP-16) 50 mg/m2 po qd x 3 weeks q4w

Johnson DH et al. Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin Oncol 1990;8:1613 (link to the article).

Paclitaxel
Paclitaxel (Taxol) 80 mg/m2 iv over 1 hour qw x 6 wks every 8 wks

Yamamoto N et al. phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer. Anticancer Res 2006; 26:777 (link to the article).

Topotecan po
Topotecan (Hycamtin) 2.3 mg/m2/d po d1-5 q3w

Eckardt JR et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol 2007; 25:2086 (link to the article).

O'Brien M et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 2006; 24:5441 (link to the article).

Topotecan iv
Topotecan (Hycamtin) 1.5 mg/m2/d iv over 30 minutes d1-5 q3w

Eckardt JR et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol 2007; 25:2086 (link to the article).

Ardizzoni A et al. Topotecan, a new active drug in the second-line treatment of small cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group. J Clin Oncol 1997; 15:2090 (link to the article).

Amrubicin 40 mg/m2/d in 20 ml of normal saline iv over 5 min d1-3 q3w

Onoda S et al. Phase II trial of amrubicin for treatment of refractory or relapsed small-cell lung cancer: Thoracic Oncology Research Group Study 0301. J Clin Oncol 2006; 24:5448 (link to the article).